The proposal is a continuation of the work of this laboratory on neurohormonal regulation of gastric activity. Three subprojects are proposed: 1. The dose-response relations and the vagal dependency of inhibition of gastric acid secretion by agents such as acid, fat, and hypertonic solutions acting in the intestine. The aim is to determine the relative importance of neural and hormonal components in inhibition of acid by agents acting in the intestine. The role of three peptides, GIP, neurotensin, and somatostatin, will be studied in detail. 2. The mechanism by which buffers at pH 8 to 9 become acidified when bathing oxyntic gland mucosa. Amino acid solutions, which are strongly buffered at pH 8 to 9, become rapidly acidified when bathing oxyntic mucosa at this pH. These studies aim to determine whether this is caused by secretion of acid by parietal cells, diffusion of carbon dioxide from blood to lumen (thereby forming carbonic acid which becomes trapped in the buffer), or some other process. 3. Development of a method for measurement of telemthylhistamine on gastric juice and blood plasma for the purpose of using it as an index of the release of gastric mucosal histamine by nonhistamine stimulants of gastric acid secretion. Parietal cells are very rich in histamine N-methyltransferase, so histamine that has stimulated parietal cells will be transformed to telemethylhistamine. By measuring this metabolite in gastric juice and gastric venous plasma, it may be possible to estimate the degree to which nonhistamine stimulants of gastric acid secretion release histamine from gastric mucosa.